Cranberry juice extract, a mild prooxidant with cytotoxic properties independent of reactive oxygen species.

A cranberry juice extract (CJE), rich in proanthocyanidins, had weak prooxidant properties, generating low levels of hydrogen peroxide (H₂O₂) and superoxide. Generation of H₂O₂ was pH dependent, increasing at alkaline pH, and was lowered in the presence of catalase and, to a lesser extent, of superoxide dismutase (SOD). Growth inhibition and cytotoxicity were noted towards human oral carcinoma HSC-2 cells, with midpoint cytotoxicity at 200 µg/mL CJE, but not towards human gingival HF-1 fibroblasts. Being a mild prooxidant, CJE toxicity was unaffected by exogenous catalase and pyruvate, scavengers of H₂O₂, but triggered intracellular synthesis of reduced glutathione, as confirmed by cell staining with Cell Tracker™ Green. The presence of exogenous SOD potentiated the toxicity of CJE, possibly by stabilizing the CJE phenols and hindering their degradative autooxidation. Conversely, 'spent' CJE, i.e. CJE added to cell culture medium and incubated for 24 h at 37 °C prior to use, was much less toxic to HSC-2 cells than was freshly prepared CJE. These differences in toxicity between SOD-stabilized CJE, freshly prepared CJE, and 'spent' CJE were confirmed in HSC-2 cells stained with aceto-orcein, which also indicated that the mode of cell death was by the induction of apoptosis.